miR‑1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells

Deng,Lang‑Mei; Tan,Tan; Zhang,Tian‑Yi; Xiao,Xue‑Fei; Gu,Huan

doi:10.3892/ijo.2019.4831

miR‑1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells

Authors:
- Lang‑Mei Deng
- Tan Tan
- Tian‑Yi Zhang
- Xue‑Fei Xiao
- Huan Gu
View Affiliations

Affiliations: Critical Care Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Inspection, Chenzhou No.1 People's Hospital, Chenzhou, Hunan 423000, P.R. China, Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
Published online on: June 25, 2019 https://doi.org/10.3892/ijo.2019.4831
Pages: 451-461
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancer‑associated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resulting in the failure of treatment. To investigate the molecular mechanism of MDR, the roles of microRNA (miR)‑1 were studied in GC. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR‑1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR‑1 on the half maximal inhibitory concentration (IC50), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dual‑luciferase assay and western blotting were used to determine the target of miR‑1 in GC. It was demonstrated that miR‑1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR‑1 in MDR GC cells decreased IC50, but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dual‑luciferase activity assay indicated that sorcin was the target of miR‑1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR‑1 in MDR GC cells. The role of miR‑1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.

View Figures

View References

1	Zhang D and Fan D: New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Future Oncol. 6:527–537. 2010. View Article : Google Scholar : PubMed/NCBI
2	Du X, Liu B, Luan X, Cui Q and Li L: miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy. Exp Ther Med. 15:599–605. 2018.PubMed/NCBI
3	Ozben T: Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett. 580:2903–2909. 2006. View Article : Google Scholar : PubMed/NCBI
4	Ma Y, Wei X and Wu Z: HNF-4α promotes multidrug resistance of gastric cancer cells through the modulation of cell apoptosis. Oncol Lett. 14:6477–6484. 2017.
5	Colotti G, Poser E, Fiorillo A, Genovese I, Chiarini V and Ilari A: Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells. Molecules. 19:13976–13989. 2014. View Article : Google Scholar : PubMed/NCBI
6	Ilari A, Johnson KA, Nastopoulos V, Verzili D, Zamparelli C, Colotti G, Tsernoglou D and Chiancone E: The crystal structure of the sorcin calcium binding domain provides a model of Ca²⁺-dependent processes in the full-length protein. J Mol Biol. 317:447–458. 2002. View Article : Google Scholar : PubMed/NCBI
7	Genovese I, Fiorillo A, Ilari A, Masciarelli S, Fazi F and Colotti G: Binding of doxorubicin to Sorcin impairs cell death and increases drug resistance in cancer cells. Cell Death Dis. 8:e29502017. View Article : Google Scholar : PubMed/NCBI
8	Deng L, Su T, Leng A, Zhang X, Xu M, Yan L, Gu H and Zhang G: Upregulation of soluble resistance-related calcium-binding protein (sorcin) in gastric cancer. Med Oncol. 27:1102–1108. 2010. View Article : Google Scholar
9	Yamagishi N, Nakao R, Kondo R, Nishitsuji M, Saito Y, Kuga T, Hatayama T and Nakayama Y: Increased expression of sorcin is associated with multidrug resistance in leukemia cells via up-regulation of MDR1 expression through cAMP response element-binding protein. Biochem Biophys Res Commun. 448:430–436. 2014. View Article : Google Scholar : PubMed/NCBI
10	Van der Bliek AM, Meyers MB, Biedler JL, Hes E and Borst P: A 22-kd protein (sorcin/V19) encoded by an amplified gene in multidrug-resistant cells, is homologous to the calcium-binding light chain of calpain. EMBO J. 5:3201–3208. 1986. View Article : Google Scholar : PubMed/NCBI
11	He Q, Zhang G, Hou D, Leng A, Xu M, Peng J and Liu T: Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp. Oncol Rep. 25:237–243. 2011.
12	Gong Z, Sun P, Chu H, Zhu H, Sun D and Chen J: Overexpression of sorcin in multidrug-resistant human breast cancer. Oncol Lett. 8:2393–2398. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yi H, Yang YX, Tang CE, Chen ZC, Zhang GY and Xiao ZQ: Sorcin overexpression and multidrug resistance in human gastric cancer cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 31:340–344. 3492006.In Chinese.
14	Xu P, Jiang YF and Wang JH: shRNA-mediated silencing of sorcin increases drug chemosensitivity in myeloma KM3/DDP and U266/ADM cell lines. Int J Clin Exp Pathol. 8:2300–2310. 2015.PubMed/NCBI
15	Hu Y, Li S, Yang M, Yan C, Fan D, Zhou Y, Zhang Y, Yagüe E and Xiong D: Sorcin silencing inhibits epithelial-to-mesenchymal transition and suppresses breast cancer metastasis in vivo. Breast Cancer Res Treat. 143:287–299. 2014. View Article : Google Scholar
16	Macfarlane LA and Murphy PR: MicroRNA: Biogenesis, function and role in cancer. Curr Genomics. 11:537–561. 2010. View Article : Google Scholar
17	Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: Rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI
18	Han C, Yu Z, Duan Z and Kan Q: Role of microRNA-1 in human cancer and its therapeutic potentials. BioMed Res Int. 2014:4283712014. View Article : Google Scholar : PubMed/NCBI
19	Xie M, Dart DA, Guo T, Xing XF, Cheng XJ, Du H, Jiang WG, Wen XZ and Ji JF: MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer. Gastric Cancer. 21:41–54. 2018. View Article : Google Scholar :
20	Li J, Guan J, Long X, Wang Y and Xiang X: mir-1-mediated paracrine effect of cancer-associated fibroblasts on lung cancer cell proliferation and chemoresistance. Oncol Rep. 35:3523–3531. 2016. View Article : Google Scholar : PubMed/NCBI
21	Liu M, Zheng S, Zhang X, Guo H, Shi X, Kang X, Qu Y, Hu Z and Tian J: Cerenkov luminescence imaging on evaluation of early response to chemotherapy of drug-resistant gastric cancer. Nanomedicine. 14:205–213. 2018. View Article : Google Scholar
22	Wang Y, Wu K, Yang Z, Zhao Q and Fan D, Xu P, Nie Y and Fan D: Multidrug-resistance related long non-coding RNA expression profile analysis of gastric cancer. PLoS One. 10:e01354612015. View Article : Google Scholar : PubMed/NCBI
23	Xu YC, Liu X, Li M, Li Y, Li CY, Lu Y, Sanches J, Wang L, Du Y, Mao LM, et al: A novel mechanism of doxorubicin resistance and tumorigenesis mediated by microRNA-501-5p-suppressed BLID. Mol Ther Nucleic Acids. 12:578–590. 2018. View Article : Google Scholar : PubMed/NCBI
24	Koontz MZ, Horning SJ, Balise R, Greenberg PL, Rosenberg SA, Hoppe RT and Advani RH: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: The Stanford University experience over three generations of clinical trials. J Clin Oncol. 31:592–598. 2013. View Article : Google Scholar : PubMed/NCBI
25	Waqar SN and Morgensztern D: Treatment advances in small cell lung cancer (SCLC). Pharmacol Ther. 180:16–23. 2017. View Article : Google Scholar : PubMed/NCBI
26	Dower CM, Bhat N, Gebru MT, Chen L, Wills CA, Miller BA and Wang HG: Targeted inhibition of ULK1 promotes apoptosis and suppresses tumor growth and metastasis in neuroblastoma. Mol Cancer Ther. 17:2365–2376. 2018. View Article : Google Scholar : PubMed/NCBI
27	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
28	Chen QN, Wei CC, Wang ZX and Sun M: Long non-coding RNAs in anti-cancer drug resistance. Oncotarget. 8:1925–1936. 2017.
29	Sui H, Cai GX, Pan SF, Deng WL, Wang YW, Chen ZS, Cai SJ, Zhu HR and Li Q: miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther. 13:3137–3151. 2014. View Article : Google Scholar : PubMed/NCBI
30	Xie M, Dart DA, Owen S, Wen X, Ji J and Jiang W: Insights into roles of the miR-1, -133 and -206 family in gastric cancer (Review). Oncol Rep. 36:1191–1198. 2016. View Article : Google Scholar : PubMed/NCBI
31	Cao W, Wei W, Zhan Z, Xie D, Xie Y and Xiao Q: Regulation of drug resistance and metastasis of gastric cancer cells via the microRNA647-ANK2 axis. Int J Mol Med. 41:1958–1966. 2018.PubMed/NCBI
32	Yan Z, Xiong Y, Xu W, Gao J, Cheng Y, Wang Z, Chen F and Zheng G: Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS One. 7:e400372012. View Article : Google Scholar : PubMed/NCBI
33	Mataki H, Enokida H, Chiyomaru T, Mizuno K, Matsushita R, Goto Y, Nishikawa R, Higashimoto I, Samukawa T, Nakagawa M, et al: Downregulation of the microRNA-1/133a cluster enhances cancer cell migration and invasion in lung-squamous cell carcinoma via regulation of Coronin1C. J Hum Genet. 60:53–61. 2015. View Article : Google Scholar
34	Chang YS, Chen WY, Yin JJ, Sheppard-Tillman H, Huang J and Liu YN: EGF receptor promotes prostate cancer bone metastasis by downregulating miR-1 and activating TWIST1. Cancer Res. 75:3077–3086. 2015. View Article : Google Scholar : PubMed/NCBI
35	Xu L, Zhang Y, Wang H, Zhang G, Ding Y and Zhao L: Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway. J Transl Med. 12:2442014. View Article : Google Scholar : PubMed/NCBI
36	Tsai KW, Hu LY, Chen TW, Li SC, Ho MR, Yu SY, Tu YT, Chen WS and Lam HC: Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer. Oncol Rep. 33:485–493. 2015. View Article : Google Scholar
37	Nasser MW, Datta J, Nuovo G, Kutay H, Motiwala T, Majumder S, Wang B, Suster S, Jacob ST and Ghoshal K: Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem. 283:33394–33405. 2008. View Article : Google Scholar : PubMed/NCBI
38	Beale PJ, Rogers P, Boxall F, Sharp SY and Kelland LR: BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma. Br J Cancer. 82:436–440. 2000. View Article : Google Scholar : PubMed/NCBI
39	Chen J, Wang L, Tang Y, Gong G, Liu L, Chen M, Chen Z, Cui Y, Li C, Cheng X, et al: Maspin enhances cisplatin chemosensitivity in bladder cancer T24 and 5637 cells and correlates with prognosis of muscle-invasive bladder cancer patients receiving cisplatin based neoadjuvant chemotherapy. J Exp Clin Cancer Res. 35:22016. View Article : Google Scholar : PubMed/NCBI
40	Hu Y, Cheng X, Li S, Zhou Y, Wang J, Cheng T, Yang M and Xiong D: Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF-7/A02 cells via regulating apoptosis-related proteins. Cancer Chemother Pharmacol. 72:789–798. 2013. View Article : Google Scholar : PubMed/NCBI
41	Gottesman MM, Fojo T and Bates SE: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI
42	Tainton KM, Smyth MJ, Jackson JT, Tanner JE, Cerruti L, Jane SM, Darcy PK and Johnstone RW: Mutational analysis of P-glycoprotein: Suppression of caspase activation in the absence of ATP-dependent drug efflux. Cell Death Differ. 11:1028–1037. 2004. View Article : Google Scholar : PubMed/NCBI
43	de Groot DJ, van der Deen M, Le TK, Regeling A, de Jong S and de Vries EG: Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1. Br J Cancer. 97:1077–1083. 2007. View Article : Google Scholar : PubMed/NCBI
44	Ye CG, Wu WK, Yeung JH, Li HT, Li ZJ, Wong CC, Ren SX, Zhang L, Fung KP and Cho CH: Indomethacin and SC236 enhance the cytotoxicity of doxorubicin in human hepatocellular carcinoma cells via inhibiting P-glycoprotein and MRP1 expression. Cancer Lett. 304:90–96. 2011. View Article : Google Scholar : PubMed/NCBI
45	Wang YH, Imai Y, Shiseki M, Tanaka J and Motoji T: Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and inhibits leukemic cell proliferation. Leuk Res. 67:99–108. 2018. View Article : Google Scholar : PubMed/NCBI
46	Tuo H, Shu F, She S, Yang M, Zou XQ, Huang J, Hu HD, Hu P, Ren H, Peng SF, et al: Sorcin induces gastric cancer cell migration and invasion contributing to STAT3 activation. Oncotarget. 8:104258–104271. 2017. View Article : Google Scholar : PubMed/NCBI